Daytrana

"The U.S. Food and Drug Administration today allowed marketing of the first medical device based on brain function to help assess attention-deficit/hyperactivity disorder (ADHD) in children and adolescents 6 to 17 years old. When used as part of "...

The most common ( ≥ 2% of subjects) adverse reaction
associated with discontinuations in double-blind clinical trials in children or
adolescents was application site reactions.

The overall Daytrana development program included
exposure to Daytrana in a total of 2,152 participants in clinical trials,
including 1,529 children aged 6-12, 223 adolescents aged 13-17, and 400 adults.
The 1,752 child and adolescent subjects aged 6-17 years were evaluated in 10
controlled clinical studies, 7 open-label clinical studies, and 5 clinical
pharmacology studies. In a combined studies pool of children using Daytrana
with a wear time of 9 hours, 212 subjects were exposed for ≥ 6 months and
115 were exposed for ≥ 1 year; 85 adolescents have been exposed for
≥ 6 months. Most patients studied were exposed to Daytrana patch sizes of
12.5 cm², 18.75 cm², 25 cm² or 37.5 cm²,
with a wear time of 9 hours.

In the data presented below, the adverse reactions
reported during exposure were obtained primarily by general inquiry at each
visit, and were recorded by the clinical investigators using terminology of
their own choosing. Consequently, it is not possible to provide a meaningful estimate
of the proportion of individuals experiencing adverse reactions without first
grouping similar types of events into a smaller number of standardized event
categories.

Throughout this section adverse reactions reported are
events that were considered to be reasonably associated with the use of
Daytrana based on comprehensive assessment of the available adverse event
information. A causal association for Daytrana often cannot be reliably
established in individual cases. Further, adverse reaction rates observed in
the clinical trials of a drug cannot be directly compared to rates in clinical
trials of another drug and may not reflect the rates observed in clinical
practice.

Clinical Trials Experience

Adverse Reactions Associated With Discontinuation of
Treatment

In a 7-week double-blind, parallel-group,
placebo-controlled study in children with ADHD conducted in the outpatient
setting, 7.1% (7/98) of patients treated with Daytrana discontinued due to
adverse events compared with 1.2% (1/85) receiving placebo. The most commonly
reported ( ≥ 1% and twice the rate of placebo) adverse reactions leading
to discontinuation in the Daytrana group were application site reaction (2%),
tics (1%), headache (1%), and irritability (1%).

In a 7-week double-blind, parallel-group,
placebo-controlled study in adolescents with ADHD conducted in the outpatient
setting, 5.5% (8/145) of patients treated with Daytrana discontinued due to
adverse reactions compared with 2.8% (2/72) receiving placebo. The most
commonly reported adverse reactions leading to discontinuation in the Daytrana
group were application site reaction (2%) and decreased appetite/anorexia
(1.4%).

Daytrana is a dermal irritant. In addition to the most
commonly reported adverse reactions presented in Table 2, the majority of
subjects in those studies had minimal to definite skin erythema at the patch
application site. This erythema generally caused no or minimal discomfort and
did not usually interfere with therapy or result in discontinuation from
treatment. Erythema is not by itself a manifestation of contact sensitization.
However, contact sensitization should be suspected if erythema is accompanied
by evidence of a more intense local reaction (edema, papules, vesicles) that
does not significantly improve within 48 hours or spreads beyond the patch site
[see WARNINGS AND PRECAUTIONS].

Most Commonly Reported Adverse Reactions

Table 2 lists treatment-emergent adverse reactions
reported in ≥ 1% Daytrana-treated children or adolescents with ADHD in
two 7 week double-blind, parallel-group, placebo-controlled studies conducted
in the outpatient setting. Overall, in these studies, 75.5% of children and
78.6% of adolescents experienced at least 1 adverse event.

Table 2 : Number (%) of Subjects with Commonly
Reported Adverse Reactions ( ≥ 1% in the Daytrana Group) in 7-Week
Placebo-controlled Studies in Either Children or Adolescents - Safety
Population

System Organ Class Preferred term

Adolescents

Children

Placebo
N = 72

Daytrana
N = 145

Placebo
N = 85

Daytrana
N = 98

Cardiac Disorders

Tachycardia

0 (0)

1 (0.7)

0 (0)

1 (1.0)

Gastrointestinal disorders

Abdominal pain

0 (0)

7 (4.8)

5 (5.9)

7 (7.1)

Nausea

2 (2.8)

14 (9.7)

2 (2.4)

12 (12.2)

Vomiting

1 (1.4)

5 (3.4)

4 (4.7)

10 (10.2)

Investigations

Weight decreased

1 (1.4)

8 (5.5)

0 (0)

9 (9.2)

Metabolism and nutrition disorders

Anorexia

1 (1.4)

7 (4.8)

1 (1.2)

5 (5.1)

Decreased appetite

1 (1.4)

37 (25.5)

4 (4.7)

25 (25.5)

Nervous system disorders

Dizziness

1 (1.4)

8 (5.5)

1 (1.2)

0 (0)

Headache

9 (12.5)

18 (12.4)

10 (11.8)

15 (15.3)

Psychiatric disorders

Affect lability

1 (1.4)

0 (0)

0 (0)

6 (6.1)*

Insomnia

2 (2.8)

9 (6.2)

4 (4.7)

13 (13.3)

Irritability

5 (6.9)

16 (11)

4 (4.7)

7 (7.1)

Tic

0 (0)

0 (0)

0 (0)

7 (7.1)

* Six subjects had affect
lability, all judged as mild and described as increased emotionally sensitive,
emotionality, emotional instability, emotional lability, and intermittent
emotional

Adverse Reactions With the
Long-Term Use of Daytrana

In a long-term open-label study
of up to 12 months duration in 326 children wearing Daytrana 9 hours daily, the
most common ( ≥ 10%) adverse reactions were decreased appetite, headache,
and weight decreased. A total of 30 subjects (9.2%) were withdrawn from the
study due to adverse events and 22 additional subjects (6.7%) discontinued
treatment as the result of an application site reaction. Other than application
site reactions, affect lability (5 subjects, 1.5%) was the only additional
adverse reaction leading to discontinuation reported with a frequency of
greater than 1%.

In a long-term open-label study
of up to 6 months duration in 162 adolescents wearing Daytrana 9 hours daily,
the most common ( ≥ 10%) adverse reactions were decreased appetite and
headache. A total of 9 subjects (5.5%) were withdrawn from the study due to
adverse events and 3 additional subjects (1.9%) discontinued treatment as the
result of an application site reaction. Other adverse reactions leading to
discontinuation that occurred with a frequency of greater than 1% included
affect lability and irritability (2 subjects each, 1.2%).

Postmarketing Experience

In addition, the following adverse reactions have been
identified during the postapproval use of Daytrana. Because these reactions are
reported voluntarily from a population of uncertain size, it is not possible to
reliably estimate their frequency or establish a causal relationship to
Daytrana exposure.

Adverse Reactions With Oral Methylphenidate Products

Nervousness and insomnia are the most common adverse
reactions reported with other methylphenidate products. In children, loss of
appetite, abdominal pain, weight loss during prolonged therapy, insomnia, and
tachycardia may occur more frequently; however, any of the other adverse
reactions listed below may also occur.

Neuroleptic Malignant Syndrome: Very rare reports
of neuroleptic malignant syndrome (NMS) have been received, and, in most of
these, patients were concurrently receiving therapies associated with NMS. In a
single report, a ten-year-old boy who had been taking methylphenidate for
approximately 18 months experienced an NMS-like event within 45 minutes of
ingesting his first dose of venlafaxine. It is uncertain whether this case
represented a drug-drug interaction, a response to either drug alone, or some
other cause.

Hypotension Agents

Human pharmacologic studies have shown that
methylphenidate may inhibit the metabolism of coumarin anticoagulants,
anticonvulsants (e.g., phenobarbital, phenytoin, primidone), and some tricyclic
drugs (e.g., imipramine, clomipramine, desipramine) and selective serotonin reuptake inhibitors. Downward dose adjustments of these drugs may be required
when given concomitantly with methylphenidate. It may be necessary to adjust
the dosage and monitor plasma drug concentrations (or, in the case of coumarin,
coagulation times), when initiating or discontinuing methylphenidate.

Drug Abuse And Dependence

Controlled Substance

Daytrana is classified as a Schedule II controlled
substance by federal regulation.